Although the important human pathogen, Streptococcus pyogenes, has been studied for many years, important questions about the pathogenesis of streptococcal diseases and the contribution of streptococcal products to these infections remain to be answered. This proposal deals with the streptococcal cytolytic toxins, streptolysin O and streptolysin S. The long-term objectives of our research are to determine precisely how these toxins affect the membranes of sensitive cells, and to understand what role, if any, the toxins play in the pathogenesis of acute streptococcal infections and in the nonsupportive sequelae of such infections. The specific aims of this proposal are first, to study the effects of both toxins on membranes and membrane constituents, using liposomes and cultures of human cells as targets of toxin action. We will examine the effects of streptolysin O on model membranes (liposomes), analyze the damaging effects of streptolysin S on cultures of human cells and study the reversability of this process, and investigate the effects of the streptococcal toxins on phagocytosis. Second, we will obtain monoclonal antibodies to streptolysin O and use them to study the structure of the toxin and to correlate structure with function. In addition, we will use the monoclonal antibodies to compare streptolysin O with the related thiol-activated cytolytic toxins.